proof of concept study of rilzabrutinib in adult patients with moderate-to-severe atopic dermatitis

Conditions: Atopic Dermatitis

Summary: this was a parallel treatment, phase 2, double-blind, 2-arm, placebo-controlled study with 2 staggered cohorts (2 arms in each cohort) to evaluate the efficacy and safety of rilzabrutinib in adult participants (aged at least 18 years) with moderate-to-severe ad and intolerance or inadequate response to topical corticosteroids (tcs). the total study duration per participant was expected to be approximately 21 weeks, including up to 4 weeks of screening, 16 weeks of on-treatment double-blind period, 1 week of post-treatment follow-up.


Eligibility criteria:
inclusion criteria: * ad as defined by the american academy of dermatology consensus criteria. * history of ad for at least 12 months prior to baseline as determined by the investigator through patient interview. * eczema area and severity index (easi) score ≥ 12 at screening and at baseline. * iga score ≥ 3 (on the 0 to 4 iga scale) at baseline. * bsa of ad involvement ≥ 10% at baseline. * documented inadequate response or intolerance to tcs within 6 months prior to baseline visit * baseline pp-nrs score for maximum itch intensity ≥4. * all contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * for optional substudy only: willingness to have 2 tape strips for comparison of baseline and treatment response. exclusion criteria: * skin comorbidities that may interfere with study assessments such as psoriasis, tinea corporis, lupus erythematosus. * conditions that may predispose the patient to excessive bleeding. * any other clinically significant disease, condition, or medical history that, in the opinion of the investigator, would interfere with participant safety, trial evaluations, and/or trial procedures. * laboratory abnormalities at the screening visit * history of serious infections requiring intravenous therapy with the potential for recurrence (as judged by the site investigator and the sponsor medical monitor), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at screening (grade 2 or higher) including active coronavirus disease 2019 (covid-19). * live vaccine except bacille calmette guerin-vaccination within 28 days prior to day 1 or plan to receive one during the trial; bacille calmette guerin-vaccination within 12 months prior to screening. * covid-19 vaccine within 14 days prior to study day 1. * refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption. * initiation of prescription moisturizers (with or without additives such as ceramide, hyaluronic acid, urea, or filaggrin), topical anesthetics or antihistamines during the screening period. * use of tcs, topical calcineurin (tacrolimus, and/or pimecrolimus) or topical phosphodiesterase 4 inhibitor within 1 week prior to baseline and as concomitant medication. * use of systemic corticosteroids within 4 weeks prior to baseline and as concomitant medication. * phototherapy for ad or regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks prior to baseline or likely to be required as concomitant procedure during the study. * use of mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous immunoglobulin (ivig), kineret (anakinra), enbrel (etanercept), or any other immunosuppressant not mentioned in this exclusion criterion within 4 weeks prior to baseline. * use of infliximab, adalimumab, golimumab, abatacept, tocilizumab, certolizumab, secukinumab, ifn-γ, jak inhibitors, dupilumab, and any other biologic or targeted-synthetic disease modifier drug not mentioned in this exclusion criterion or in exclusion criterion, as well as plasmapheresis within 12 weeks prior to baseline. * use of anti-cd20 drugs such as rituximab, ofatumumab, other long-acting biologics within 6 months prior to baseline (or shorter if there is documented b cell reconstitution for anti-cd20 drugs). * use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of baseline (it is acceptable to change participant to h2 receptor blocking drugs prior to baseline). * concomitant use of known systemic strong-to-moderate inhibitors and inducers of cytochrome p450 3a (cyp3a) within 14 days or 5 half-lives (whichever is longer) prior to baseline. * previous use of a btk inhibitor. * had received any investigational drug (or is currently using an investigational device) within the 30 days before baseline, or at least 5 times the respective elimination half-life time (whichever is longer). * active tb or a history of incompletely treated tb, quantiferon positive patients, clinically significant abnormality consistent with prior/active tb infection based upon chest radiograph with at least posterior-anterior view, suspected extrapulmonary tb infection, or patients at high risk of contracting tb. the above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.